Search Results (4,971)

Chronic hyperglycemia inflicts serious cellular damage by inducing oxidative stress through the excessive production of free radicals. This oxidative milieu may impair the cellular redox capacity and disrupt the insulin-like growth factor (IGF) system, thereby increasing the risk of cardiovascular complications. This study aimed to investigate plasma levels of components of the IGF system and antioxidant biomarkers in young adults with type 1 diabetes mellitus (T1DM) compared to age-matched healthy controls in Brazil. This study included 129 patients with T1DM (76 female, 53 male; mean age 26.97 ± 0.6 years) and 95 healthy controls (61 female, 34 male; mean age 27.35 ± 0.68 years). Young Brazilian adults with T1DM had significantly lower mean IGF-I and higher mean IGFBP-1 levels compared to healthy controls. The T1DM group showed a more atherogenic profile, characterized by a significantly elevated ApoB/ApoA1 ratio and increased oxidized LDL levels. However, a subset of patients with significantly better glycemic control exhibited serum IGF-I and IGFBP-1 levels within the normal range observed in controls, which may indicate the presence of residual functional beta-cell activity or reflect better glycemic control in this subgroup. Antioxidant components and oxidative stress biomarkers were significantly upregulated in the T1DM group compared to the control group, suggesting a compensatory adaptive response. No significant correlation was observed between biomarkers of oxidative stress and the IGF-system. Full article

Metallic implants used in orthopedics, such as titanium alloys, possess excellent mechanical strength but suffer from corrosion and poor bio-integration, often necessitating revision surgeries. Bioactive coatings, particularly hydroxyapatite, can enhance implant osteoconductivity, but high-purity synthetic hydroxyapatite is costly. This study investigates the development and characterization of a low-cost, biocompatible coating using hydroxyapatite derived from an unconventional natural source dromedary bone applied onto a titanium substrate via plasma spraying. Hydroxyapatite powder was synthesized from dromedary femurs through a thermal treatment process at 1000 °C. The resulting powder was then deposited onto a sandblasted titanium dioxide substrate using an atmospheric plasma spray technique. The physicochemical, structural, and morphological properties of both the source powder and the final coating were comprehensively analyzed using Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, X-ray Diffraction, and Fourier-Transform Infrared Spectroscopy. Characterization of the powder confirmed the successful synthesis of pure, crystalline hydroxyapatite, with Fourier-Transform Infrared Spectroscopy analysis verifying the complete removal of organic matter. The plasma-sprayed coating exhibited good adhesion and a homogenous, lamellar microstructure typical of thermal spray processes, with an average thickness of approximately 95 μm. X-ray Diffraction analysis of the coating revealed that while hydroxyapatite remained the primary phase, partial decomposition occurred during spraying, leading to the formation of secondary phases, including tricalcium phosphate and calcium oxide. Scanning Electron Microscopy imaging showed a porous surface composed of fully and partially melted particles, a feature potentially beneficial for bone integration. The findings demonstrate that dromedary bone is a viable and low-cost precursor for producing bioactive hydroxyapatite coatings for orthopedic implants. The plasma spray method successfully creates a well-adhered, porous coating, though process-induced phase changes must be considered for biomedical applications. Full article

Pollen tube growth entails complex molecular interactions between the cytoskeletal apparatus and membrane trafficking. Tip growth involves polarized distribution of proteins and lipids along the plasma membrane, including liquid-ordered microdomains, rich in sterols and sphingolipids (lipid rafts), in the apical/subapical region of tobacco pollen tubes. Intriguingly, biochemical characterization of detergent-insoluble membranes purified from tobacco pollen tubes revealed the presence of both actin and tubulin. Here, we report that inhibition of sterol biosynthesis altered lipid rafts and lowered the association of tubulin with detergent-insoluble membranes. Our results showed that sterol depletion increased the number of microtubules in the subapical region, altered microtubule distribution and affected microtubule bundling activity. Oryzalin washout experiments also suggested that lipid-ordered domains could play a role in regulating microtubule nucleation/regrowth. Full article

EuPRAXIA@SPARC_LAB is an FEL (Free-Electron Laser) user facility currently under construction at INFN-LNF in the framework of the EuPRAXIA collaboration. The electron beam will be accelerated to 1 GeV by an X-band RF linac followed by a plasma wakefield acceleration stage. This high-brightness linac requires diagnostic devices able to measure the beam parameters with high accuracy and resolution. To monitor the beam energy and its spread, magnetic dipoles and quadrupoles will be installed along the linac, in combination with viewing screens and CMOS cameras. Macroparticle beam dynamics simulations have been performed to determine the optimal energy measurement setup in terms of accuracy and resolution. Similar diagnostics evaluations have been carried out for the spectrometer installed at the 100 MeV RF linac of the radioactive beam facility SSRIP (IFIN-HH, Romania), whose commissioning, foreseen for 2026, will be performed by INFN-LNF in collaboration with IFIN-HH. Optics measurements have been performed to characterize the resolution and magnification of the optical system that will be used at SSRIP, and probably also at EuPRAXIA@SPARC_LAB, for beam energy monitoring. Full article

Angioedema (AE) is a heterogeneous condition characterized by acute, localized, non-pitting edema of the skin, mucosa, and submucosal tissues, with potentially life-threatening airway involvement. This comprehensive review aims to provide an updated overview of the different AE subtypes, their pathogenesis, clinical presentation, diagnostic criteria, therapeutic strategies, and dental implications. A literature search of PubMed, MEDLINE, and Google Scholar was performed for articles published between 1950 and 2025, focusing on both bradykinin- and histamine-mediated forms. The findings highlight the importance of distinguishing histaminergic AE, which typically responds to antihistamines, corticosteroids, and epinephrine, from bradykinin-mediated AE, which requires targeted therapies such as C1 esterase inhibitor (C1-INH), icatibant, or kallikrein inhibitors. Subtypes including hereditary, acquired, and drug-induced AE are reviewed, with emphasis on diagnostic markers (C4, C1-INH, C1q) and recent genetic insights in HAE-nC1INH. In dental and surgical settings, invasive procedures may act as triggers, making prophylaxis with plasma-derived C1-INH and stress management strategies essential. In conclusion, accurate subtype recognition is crucial to guide therapy and perioperative care, and further research is needed to refine diagnostic algorithms and preventive strategies. Full article

This work investigates the influence of spark plasma sintering (SPS) parameters on the microstructure and mechanical properties of consolidated aluminum powders processed by high-energy ball milling under an air atmosphere. Sintering was performed under vacuum at various temperatures ranging from 550 °C to 625 °C and under pressures between 50 and 100 MPa. The particle size, crystallite size, and microstructure of the powders and the consolidated pellets were analyzed using laser granulometry, X-ray diffraction (XRD), scanning electron microscopy (SEM), and Archimedes’ density measurements. Mechanical properties were evaluated via Vickers microhardness, nanoindentation, and tribological testing. For comparison, unmilled aluminum powders were also consolidated and characterized. After 46 h of milling, the aluminum crystallite size was reduced from 74 nm to 68 nm. The sample’s density increased with higher sintering temperature and pressure. The aluminum sintered at 600 °C and 100 MPa after 46 h of milling exhibited the highest microhardness (187.5 HV). Nanoindentation tests were conducted to characterize different microstructural regions formed after SPS, revealing two distinct zones: one hard and one soft. The tribology results revealed that the SPS-consolidated samples of milled powders exhibited a reduction of 50% in specific wear rate and a reduction of 20% in the coefficient of friction compared to the SPS-sintered samples of unmilled powders. Full article

The therapeutic clotting factor VIII (FVIII) is known for its particular immunogenicity, with nearly 30% of hemophilic patients developing neutralizing antibodies against the infused protein. The root cause of this immunogenicity is still not well understood, but intrinsic factors, such as FVIII byproducts, have been linked to the immunological response elicited. Bioengineering of the FVIII molecule has been improving its recombinant (rhFVIII) production in many aspects, mainly enhancing its expression and stability. Assessment of immunogenicity for novel recombinant isoforms is crucial for further development and scaling-up processes, particularly due to the unpredictable antigenic properties and their impact on neutralizing antibody formation. In the present study, we describe a bioengineered human recombinant FVIII (rhFVIII-H6A), which induces lower immunogenicity in a murine model of hemophilia A. The rhFVIII-H6A product is characterized by a B-domain-deleted heavy chain (HCh), with the C-terminal of the B-domain fused to the light chain (BΔ-LCh). Compared to plasma-derived FVIII (pdFVIII) and rhFVIII reference products, treating hemophilic mice with rhFVIII-H6A induced lower levels of anti-FVIII antibody formation, including those with inhibitory neutralizing activity, while no difference was observed in the functional activity of rhFVIII-H6A in reverting the in vivo hemophilia phenotype. In addition, our results indicate that deleting the major part of the B-domain from the HCh might lower the immunogenicity of novel rhFVIII products. Full article

Apatite is a key indicator mineral whose chemical signature can reveal the genesis and evolution of ore-forming systems. However, correctly interpreting these signatures requires a robust discrimination between apatite types formed by different geological processes, such as metamorphism and hydrothermal activity. This study aims to chemically characterize and genetically classify apatite samples from the Slyudyanka deposit (Siberia, Russia) to establish discriminative geochemical fingerprints for metamorphic and hydrothermal apatite types. We analyzed 80 samples of apatite using total reflection X-ray fluorescence (TXRF) and inductively coupled plasma mass spectrometry (ICP-MS). The geochemical data were processed using principal component analysis (PCA) and k-means cluster analysis to objectively discriminate the apatite types. Our analysis reveals three distinct geochemical groups. Metamorphic veinlet apatite is defined by high U and Pb, low REE, Sr, and Th, and suprachondritic Y/Ho ratios. Massive metamorphic apatite from silicate–carbonate rocks shows extreme REE enrichment and chondritic Y/Ho ratios. Hydrothermal–metasomatic apatite features high Sr, Th, and As, with intermediate REE concentrations and chondritic Y/Ho ratios. Furthermore, we validated the critical and anomalous Y concentrations in the metamorphic veinlet apatite by cross-referencing TXRF and ICP-MS data, confirming the reliability of our measurements for this monoisotopic element. We successfully established diagnostic geochemical fingerprints that distinguish apatite formed in different geological environments at Slyudyanka. The anomalous Y/Ho ratio in metamorphic veinlet apatite serves as a key discriminant and provides insight into specific fractionation processes that occurred during the formation of phosphorites in oceanic environments, which later transformed to apatites during high-grade metamorphism without a change in the Y/Ho ratio. This work underscores the importance of multi-method analytical validation for accurate geochemical classification. Full article

Haemonchus contortus is a blood-feeding gastrointestinal nematode that significantly impacts the health and productivity of small ruminants. The burden of parasitism and the escalating incidence of anthelmintic resistance necessitate alternative control methods. Here, we characterize the enzymatic activities of five mammalian cell-expressed recombinant H. contortus cysteine proteases (HcCPs), which include two cathepsin B-like proteins (HcCBP1 and HcCBP2) and three cysteine protease 1 proteins (HcCP1a, HcCP1b, and HcCP1c). We hypothesize that these enzymes degrade host blood proteins, thereby facilitating the parasite’s nutrient acquisition and survival. Using synthetic cathepsin (cat) substrates, we show that HcCBP2 was the only protein that exhibited high catB/L but low catB or catK activity, which was inhibited by the cysteine protease inhibitor E-64. All mHcCPs degraded fibrinogen (Fg), which led to delayed plasma clotting, reduced clot density, and lysed plasma clots. All HcCPs partially degraded hemoglobin (Hb), except for mHcCBP2, which degraded Hb and bovine serum albumin completely and bovine IgG partially in the presence of a reducing agent. In conclusion, by sustaining blood feeding and facilitating immune evasion and nutrient acquisition, the HcCPs may play an essential role in the parasite’s survival. Thus, vaccines or cysteine protease inhibitors targeting these parasitic enzymes may mitigate or prevent infections. Full article

Background/Objectives: Plant-derived diuretics are attracting increasing interest due to their promising efficacy and improved safety profile compared with synthetic drugs. This study aimed to characterize the phytochemical composition of Astragalus boeticus (A. boeticus) extracts, evaluate their diuretic activity, and assess the oral safety of their main phenolic compound. Methods: Aqueous (AQE) and hydroethanolic (EtOHE) extracts were analyzed using LC–MS/MS, while in silico toxicity prediction of trans-resveratrol was performed using ProTox-II and ADMETlab 2.0. Diuretic activity was evaluated in male Wistar rats (n = 24) divided into four groups: control (distilled water, 10 mL/kg), furosemide (10 mg/kg), AQE (300 mg/kg), and EtOHE (300 mg/kg). Urine and plasma samples were collected after 15 days to determine electrolyte concentrations, creatinine level, creatinine clearance, and hepatic enzyme profile. Results: LC–MS/MS profiling identified fourteen phenolic compounds, with trans-resveratrol (270 µg/g in AQE) being the most abundant, followed by cyanidin-3-O-glucoside and gentisic acid. In silico assessments revealed no hepatotoxic, mutagenic, or neurotoxic effects of trans-resveratrol. Both extracts significantly enhanced urinary output, chloride excretion, and creatinine clearance, while maintaining stable renal and hepatic biochemical parameters, indicating potent diuretic activity without toxicity. Conclusions: A. boeticus extracts demonstrate strong diuretic potential associated with a favorable safety profile, likely linked to their phenolic composition dominated by trans-resveratrol. These findings support the use of A. boeticus as a natural and safe diuretic source. Further investigation is recommended to elucidate its pharmacological mechanisms and therapeutic relevance. Full article

Background: Hypertriglyceridemia is a lipid disorder characterized by elevated plasma triglyceride levels, and its prevalence increases with aging. This condition contributes substantially to morbidity and mortality in older adults. In settings with limited access to laboratory testing, especially in developing countries such as Brazil, identifying low-cost and easily applicable screening tools is essential. Objective: To investigate the discriminatory capacity of anthropometric indicators of obesity for screening hypertriglyceridemia in older adults. Methods: A population-based cross-sectional study was conducted with 223 community-dwelling older adults (57% women). Independent variables included body mass index (BMI), waist circumference (WC), abdominal circumference (AC), triceps skinfold thickness (TSF), body adiposity index (BAI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and conicity index (CI). Hypertriglyceridemia was defined as triglyceride levels ≥ 150 mg/dL. Discriminatory performance was assessed using receiver operating characteristic (ROC) curves, and associations were examined using Poisson regression with robust variance. Results: The prevalence of hypertriglyceridemia was 35%. Among older men, AC and CI showed the highest sensitivities (88.90% and 77.40%), while WHR and BMI demonstrated the highest specificities (83.10% and 76.90%). In older women, AC and BMI had the highest sensitivities (95.70% and 87.20%), whereas CI and WHtR exhibited the highest specificities (72.50% and 68.80%). All anthropometric indicators were positively associated with hypertriglyceridemia after adjustment for confounders. Conclusions: AC and CI demonstrated the strongest discriminatory capacity for screening older men with a higher probability of presenting hypertriglyceridemia, while AC and BMI showed the greatest discriminatory capacity among older women. In contrast, WHR and BMI had the highest ability to rule out the condition in older men, whereas CI and WHtR performed this role more effectively in older women. These findings show that low-cost anthropometric indicators can be used in a complementary manner, combining the most sensitive and the most specific measures to support an optimized triage process for hypertriglyceridemia in older adults, particularly in resource-limited settings. Full article

As a primary macronutrient, nitrogen is integral to plant growth and regulates their development; ammonium transporters (AMTs) mediate nitrogen absorption and its involvement in metabolism. In this study, nine BcAMT genes were identified in flowering Chinese cabbage (Brassica campestris) and were systematically categorized into two subfamilies. Their evolutionary relationships, conserved motifs, chromosomal distribution, cis-regulatory elements, and expression profiling were systematically characterized. RNA sequencing and quantitative real-time PCR (qRT-PCR) analyses demonstrated that BcAMT1.1 was abundantly expressed in roots, leaves, and stems of flowering Chinese cabbage and was markedly upregulated under nitrogen deficiency. Assessing subcellular location using GFP fusion demonstrated that BcAMT1.1 localized to the plasma membrane. Functional assays identified heterologous expression in the yeast mutant strain 31019b, and transgenic Arabidopsis validated that BcAMT1.1 acted as a functional ammonium transporter. Compared with the wildtype, overexpressing BcAMT1.1 promoted seedling growth, enhanced NH₄⁺ influxes and NO₃⁻ effluxes under low-nitrogen conditions, and significantly increased the transcription levels of key nitrogen assimilation genes (i.e., AtGLN1.1, AtGLN2, AtGDH2). Collectively, our findings enhance the fundamental understanding of BcAMT gene functions and highlight BcAMT1.1 as a crucial component in nitrogen uptake and assimilation under low-nitrogen conditions, providing valuable genetic resources for improving nitrogen efficiency in vegetable crops. Full article

(1) Background: Platelet-rich plasma (PRP) therapy has become a cornerstone of equine regenerative medicine, yet significant methodological variability compromises reproducibility and clinical comparability. (2) Methods: This scoping review systematically mapped and analyzed peer-reviewed studies describing equine PRP preparation methods and commercial systems (2000–2024) following PRISMA-ScR guidelines. (3) Results: Twenty-four studies met the inclusion criteria, encompassing 317 horses and both manual and commercial devices. Double-spin manual protocols predominated, though centrifugation parameters, anticoagulants, and activation strategies varied widely. Methodological quality, assessed using an adapted nine-criterion framework, revealed that only 29% of studies achieved comprehensive reporting, particularly lacking platelet-yield and activation details. An additional multilingual web search identified 24 veterinary PRP kits, of which only 10 had published validation in horses, exposing a pronounced gap between marketing claims and scientific evidence. (4) Conclusions: These discrepancies underscore the need for standardized reporting, transparent characterization, and independent evaluation of PRP systems. The proposed framework aims to guide future research toward reproducible, evidence-based practices that enhance therapeutic reliability and clinical translation in equine regenerative medicine. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in PKD1 or PKD2 genes, encoding polycystin-1 (PC1) or polycystin-2 (PC2), respectively, characterized by excessive cell proliferation and fluid secretion, resulting in renal cyst formation and growth. PC1 and PC2 form a complex localized on the plasma membrane, endoplasmic reticulum, and primary cilia. PC2 is a non-selective cation channel which, in renal epithelial cells, contributes to calcium transport and signaling. It has been previously shown in renal cells that high external calcium increases whole-cell currents likely mediated by PC2. In this study, we explored the possibility that the Calcium Sensing Receptor (CaSR) is involved in the functional regulation of PC2. To test this hypothesis, human conditionally immortalized Proximal Tubular Epithelial cells, isolated from urine sediments, wt or with stably downregulated PKD1 (PC1KD) or PKD2 (PC2KD) were used. Interestingly, CaSR and PC2 co-immunoprecipitated and Proximity Ligation Assay demonstrated a direct physical interaction at endogenous protein levels. Membrane potential measurements demonstrated that selective CaSR activation, elicited by the calcimimetic R568, caused plasma membrane depolarization, consistent with the modulation of PC2-mediated cation currents, which was significantly lower in PC2KD with respect to wt and PC1KD cells. To conclude, this study provides evidence for a functional coupling of CaSR and PC2, which might be relevant for therapeutic strategies to correct dysregulations occurring in ADPKD. Full article

Migraine is characterized by severe pain and somatic symptoms like allodynia and photophobia, driven by neuroinflammation that sensitizes the trigeminal vascular system (TVS). This study investigated how neuroinflammation induced by systemic lipopolysaccharide (LPS) affects migraine-related nociceptive signaling. Using a chronic migraine model in rats with nitroglycerin (NTG), we compared prenatal and acute postnatal LPS administration. Rats with prenatal LPS exhibited lower mechanical thresholds and enhanced allodynia and photophobia after NTG. Acute LPS also increased allodynia, but not photophobia. Both LPS groups showed increased mast cell degranulation in the dura mater. Plasma CGRP after NTG administration was elevated in the acute LPS group. Electrophysiology revealed enhanced trigeminal afferent responses to serotonin in both acutely and prenatally LPS-treated rats. Calcium imaging demonstrated increased neuronal responses to serotonin and capsaicin, suggesting an upregulation of serotonin and TRPV1 receptors. Our findings show that LPS-induced neuroinflammation, whether prenatal or acute, promotes sensitization of peripheral and central nociceptive pathways, involving serotoninergic mechanisms. Full article